We propose to explore the possibility of developing a predictive cell culture assay system for the chemotherapy of human malignancies. We chose human acute leukemia as the first model since it is one of the fastest growing human neoplasms. The differential effects of chemotherapeutic agents independently assessed for normal hemopoietic and leukemic cells using clonal cell culture techniques may provide a better screening system for effective agents in human leukemia and furthermore, help in the individualization of leukemia therapy. We propose to accomplish two specific objectives: (a) to investigate the effects, both in vivo and in culture of cancer chemotherapeutic agents on human granulopoietic precursor cells from marrow and peripheral blood, using clonal cell culture techniques; and (b) to develop a reliable clonal cell culture assay for human acute leukemia cells using modifications of a double-agar layer cell culture technique. Direct studies of human hemopoietic precursor cells proposed in section (a) will yield useful information in development of less toxic and hence, more effective modes of treatment, not only for acute leukemia but also for other human malignancies. With the development of a consistent clonal cell culture assay for human acute leukemia cells as proposed in (b), the possibility to test drugs in culture for their effects on human leukemia cells will be examined in the future proposal.